P1572: IMPACT OF GUT COLONIZATION BY GRAM NEGATIVE MULTIRESISTANT BACTERIA IN PATIENTS WITH ACUTE LEUKEMIA UNDERGOING INTENSIVE ANTINEOPLASTIC TREATMENT
Authors: C. Castañon Fernandez, P. López Ugarriza, A. Fernández Moreno, N. Diaz Varela, A. M. Fernández Verdugo, J. Fernández, W. J. Zambrano, L. Escalada, P. C. Tamayo, T. Bernal del Castillo
Journal: HemaSphere (2022)

Background: Gut colonization by Gram negative multiresistant bacteria (GNMRB) occurring during chemotherapy treatment for acute leukemia (AL) reduces overall survival (OS) by increasing early non-relapse mortality (NRM). The impact of colonization once patients have finished antineoplastic treatment is unknown. Aims: To evaluate long-term consequences of GNMRB colonization on AL surviving patients. Methods: Retrospective study including all consecutive AL patients treated with standard intensive chemotherapy with or without Hematopoietic Stem Cell Transplant (HSCT) who completed first line antineoplastic treatment. A landmark analysis was performed including all patients alive 60 days after last chemotherapy cycle of HSCT. Primary end point was OS. Secondary end points were non-relapse mortality (NRM) and acute (a) and chronic (c) Graft Versus Host Disease (GVHD) in allogeneic transplanted patients. Data are presented as median (interquartile range) or proportion. Cumulative incidence of NRM was calculated accounting for the competing risk of leukemic-death. Survival curves were built using the Kaplan-Meir method and univariate analysis was performed using the Log-Rank test. Statistical analysis was performed using the R 4.1.1 software package. Results: From April 2016 to March 2021, 142 patients from a single center were treated with intensive chemotherapy, of whom 96 were alive 60 days after chemotherapy or HSCT. Median age was 55 (42-52) years with 50% (48/96) of female patients. ECOG performance status at diagnosis of the disease was 0-1 in 98% (94/96) patients. A diagnosis of Acute Myeloid Leukemia (AML), high-risk Myelodysplastic Syndrome and Acute Lymphoblastic Leukemia (ALL) was present in 85% (82/96), 1% (1/96) and 14 (14/96) patients, respectively. Hematopoietic Transplant Comorbidity Index (HCTCI) was low, intermediate and high in 68% (66/96), 16% (16/96) and 16% (16/96) patients, respectively. Within AML patients, ELN17 genetic risk was favourable, intermediate and adverse in 48% (38/79), 18% (14/79) and 34% (27/79) patients. Prophylactic fluoroquinolones were used in 65% (62/96) patients, significantly more used in AML/MDS than in ALL patients: 69% (57/83) vs 38% (5/13), respectively, P=0.03. Throughout the first line treatment, 48% (46/96) patients were colonized by GNMRB, being the recovered microorganisms: Klebisella sp. 61% (28/46), Enterobacter sp: 17%, (8/46), Citrobacter sp: 11% (5/46), E. Coli: 9% (4/46), and Pseudomonas aeruginosa 2% (1/46). With a median follow up of 17 (7-34) months, there were no differences in univariate analysis of OS between colonized compared to non-colonized patients: [53 months (95% CI: 26-NR) vs NR (95% CI: 26-NR), P= 0.9], (Figure). On the contrary, age and ELN17 genetic risk were significantly associated with OS (Table). Additionally, no differences in aGVHD [34% (10/29) vs 45% (10/22)], P=0.4, or cGVHD [18% (4/22) vs 14% (4/29), P=0.9] were observed between colonized and non-colonized patients. Regarding NRM, a non-significant increase in non-leukemic deaths were observed in colonized patients compared to non-colonized patients: 15% (7/46) vs 8% (4/46) P= 0.6. - Overall Survival Yes No P Age>65 yo 24.6 (12-NR) NR (53-NR) 0.01 ELN genetic risk 0.001 - Favorable NR (NR-NR) - - Intermediate 20.6 (6.8-NR) - - Adverse 26.6 (17.7-NR) Colonization 53.2 (26-NR) NR (26-NR) 0.9 Image:Summary/Conclusion: Gram negative multiresistant bacteria gut colonization is not associated with worse long-term outcomes in acute leukemia patients compared to non-colonized patients.